In the prior art, when L-lysine is produced by a fermentative method, a microbial strain separated from the natural environment or an artificial mutant strain obtained from such a microbial strain is used in order to improve the productivity. A large number of artificial mutant strains producing L-lysine are known. Most of them are S-2-aminoethylcysteine (AEC) resistant mutant strains, and belong to the genus of Brevibacterium, Corynebacterium, Bacillus or Escherichia. Further, various techniques have been disclosed for increasing amino acid production, for example, by employing a transformant using recombinant DNA (U.S. Pat. No. 4,278,765).
With respect to those belonging to the genus Escherichia, for example, Japanese Patent Application Laid-open No. 56-18596, U.S. Pat. No. 4,346,170, and Applied Microbiology and Biotechnoloay, 15, 227-231 (1982) describe methods of producing L-lysine using a bacterial strain in which dihydrodipicolinate synthase (hereinafter sometimes abbreviated as "DDPS") is enhanced. However, DDPS used in these cases is a wild type, which suffers feedback inhibition by L-lysine. Thus sufficiently satisfactory L-lysine productivity has not been obtained. Incidentally, Applied Microbiology and Biotechnology, 15, 227-231 (1982) mentioned above is describes an L-lysine production of 3 g/l of L-lysine hydrochloride from 75 g/l of glucose, wherein a consumption coefficient (number of g of L-lysine produced from 1 g of sugar, or percentage thereof) is calculated to be 0.04, or 4%.
On the other hand, Korean Patent Publication No. 92-8382 describes a method of producing L-lysine using a bacterium belonging to Escherichia to which DDPS originating from a bacterium belonging to the genus Corynebacterium, which is known not to suffer feedback inhibition by L-lysine (consumption coefficient: 17%), is introduced. However, the upper limit temperature for growth of bacteria belonging to the genus Corynebacterium is lower than the upper limit temperature for growth of bacteria belonging to the genus Escherichia by about 10 degrees. Thus it seems that cultivation should be performed at a lowered cultivation temperature if DNA coding for DDPS originating from a bacterium belonging to the genus Corynebacterium is introduced into a bacterium belonging to the genus Escherichia in order to utilize it for L-lysine production. Therefore, it is anticipated that it is difficult to exhibit advantages possessed by the bacterium belonging to the genus Escherichia that the growth temperature is high, the growth speed is fast, and the L-lysine-producing speed is also fast. Generally, when a gene originating from a heterologous organism is expressed, there are occasionally caused decomposition of an expression product by protease and formation of an insoluble inclusion body, in which more difficulties are anticipated as compared with a case of expression of a homologous gene. Further, when DNA coding for DDPS originating from a bacterium belonging to the genus Corynebacterium is introduced into a bacterium belonging to the genus Escherichia to industrially produce L-lysine, more strict regulation is obliged as compared with a case of use of a recombinant to which a homologous gene is introduced, in accordance with the recombinant DNA guideline.
By the way, the dihydrodipicolinate synthase (DDPS) is an enzyme for dehydrating and condensing aspartosemialdehyde and pyruvic acid to synthesize dihydrodipicolinic acid. This reaction is located at an entrance into a branch to proceed to an L-lysine biosynthesis system in biosynthesis of amino acids of the aspartic acid family. This enzyme is known to be in charge of an important regulatory site as aspartokinase is in bacteria belonging to the genus Escherichia.
DDPS is encoded by a gene called dapA in E. coli (Escherichia coli). The dapA has been cloned, and its nucleotide sequence has been also determined (Richaud, F. et al., J. Bacteriol., 297 (1986)).
On the other hand, aspartokinase (hereinafter sometimes abbreviated as "AK") is an enzyme for catalyzing a reaction to convert aspartic acid into .beta.-phosphoaspartic acid, which serves as a main regulatory enzyme in a biosynthesis system of amino acids of the aspartic acid family. AK of E. coli has three types (AKI, AKII, AKIII), two of which are complex enzymes with homoserine dehydrogenase (hereinafter sometimes abbreviated as "HD"). One of the complex enzymes is AKI-HDI encoded by a thrA gene, and the other is AKII-HDII encoded by a metLM gene. AKI is subjected to concerted suppression by threonine and isoleucine and inhibited by threonine, while AKII is suppressed by methionine.
On the contrary, it is known that only AKIII is a simple function enzyme, which is a product of a gene designated as lysC, and is subjected to suppression and feedback inhibition by L-lysine. The ratio of their intracellular activities is AKI:AKII:AKIII=about 5:1:4.
As described above, DDPS originating from bacteria belonging to the genus Corynebacterium is not subjected to feedback inhibition by L-lysine. However, when it is introduced into a bacterium belonging to the genus Escherichia to utilize it for L-lysine production, a problem arises in the cultivation temperature. It is expected that L-lysine can be efficiently produced by fermentation by using a bacterium belonging to the genus Escherichia if a mutant enzyme of DDPS or AKIII originating from a bacterium belonging to the genus Escherichia, which is not subjected to feedback inhibition by L-lysine, can be obtained. However, there is no preceding literature which describes such a mutant enzyme of DDPS, and although there is one report on a mutant enzyme of AKIII (Boy, E., et al., J. Bacteriol., 112, 84 (1972)) no example has been known which suggests that such a mutant enzyme may improve productivity of L-lysine.